Primary Parathyroid Hyperplasia Research Articles

Multiple endocrine neoplasia 2A with RET mutation p.Cys380Arg (GRCh38): A case report

MEN 2A is a complex autosomal dominant inherited syndrome characterized by pheochromocytoma (PC), medullary thyroid carcinoma (MTC) and primary parathyroid hyperplasia (PHP). We report a case of 26 years old female offended with bilateral pheochromocytoma, medullary thyroid carcinoma and primary hyperparathyroidism due to multiple endocrine neoplasia type 2A confirmed by RET gene mutation p.Cys380Arg according to the GRCh38 (Genome Reference Consortium Humain Build 38 Organism - 2013) classification. The mutation with a change of amino acid 380 from Cys (Cysteine) to Arg (Arginin) is found in more than one-half of kindreds with MEN2A.

Metastatic Thyroid Cancer After Thyroidectomy in Patient With Neuroendocrinal Tumor

Abstract Background: Multiple endocrine neoplasia type 2 is an autosomal dominant disorder with an estimated prevalence of 1 per 30,000 in the general population. Classical multiple endocrine neoplasia 2A is the most common variant. It is a heritable predisposition to medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia. The respective frequency of these tumors in classical MEN2A is over 90 percent for MTC, approximately 10 to 50 percent for pheochromocytoma, and 10 to 20 percent for multigland parathyroid hyperplasia. Discussion: our interesting patient is a 67-year-old patient with past medical history of prophylactic total thyroidectomy at the age of 25 years after a positive pentagastrin test (sister was diagnosed with MTC, pheochromocytoma),niece with metastatic kidney cancer.at that time, patient had benign pathology. Patient presented to the ED with a complain of shortness of breath after being referred by her PCP for evaluation of possible pneumonia. In the ED, her vitals were within normal, chest X-ray was done and didn’t show pneumonia but the patient was found to have elevated procalcitonin of 22.7 ng/mL(0.09 ng/mL) CT chest was done and showed enlarged necrotic cervical lymphadenopathy which was confirmed by obtaining CT of the neck. Patient had right cervical LN core biopsy, pathology was positive for medullary thyroid cancer with Immunohistochemical studies positive for TTF-1, chromogranin, synaptophysin and calcitonin, testing for pheochromocytoma came back within normal, CEA 70.7ng/ml (<0.25 ng/ml), calcitonin 2949 pg/ml (5 pg/mL) Chromogranin was high at 453 ng/ml (25 - 140 ng/mL) had PET CT with multiple low right cervical and supraclavicular lymph nodes with internal calcifications and abnormal FDG activity, which were suspicious for medullary thyroid cancer metastases, she eventually had radical neck dissection with pathology from inferior parathyroid gland positive for medullary thyroid cancer and 12/15 regional LN positive for malignancy, after the procedure her calcitonin dropped nicely to 194pg/ml, CEA dropped to 4.0, chromogrannin to 394, she was referred to genetic testing and tested positive for pathogenic variant within RET (c.1859G>T, p.Cys620Phe), which is known to be associated with multiple endocrine neoplasia type 2A, she is currently being evaluated for Lutathera treatment. Conclusion: In contrast to MEN1, in which the long-term benefit of early diagnosis by genetic screening is not well established, early diagnosis by screening of “at-risk” family members in MEN2 with positive RET mutation kindreds is essential because MTC is a life-threatening disease that can be cured or prevented by early thyroidectomy. Total thyroidectomy has been recommended for patients as young as 3 years for MEN2A if they contain the genetic mutation.

Molecular profile of parathyroid tissues and tumours: a heterogeneous landscape.

Advances in laboratory diagnostics and surgical treatment ofprimary hyperparathyroidism have ensured solid basis for research in parathyroid pathology in order to specify key molecules in pathogenesis and morphological diagnostics ofdifficult cases. Theaim ofthis study was to assess themolecular landscape and its heterogeneity in primary parathyroid hyperplasia (PPH) and adenoma, compared to carcinoma and normal glands. In aretrospective analysis of179 surgically removed parathyroid glands (102 adenomas; 27 PPH; 45 normal glands; 5 carcinomas), expression ofKi-67, p21, p27, p53, cyclin D1, Bcl-2 protein, vimentin, cytokeratin (CK) 19, E-cadherin, CD56, CD44 and parafibromin was detected by immunohistochemistry, followed by computer-assisted assessment ofmean values and heterogeneity measures. Descriptive statistics and Kruskal-Wallis test were applied. Significant differences were disclosed regarding themean and highest fraction ofKi-67 (both p < 0.001), p21 (both p < 0.001), cyclin D1 (p = 0.002) and p27-expressing cells (p = 0.010). Proliferative lesions (PPH, adenoma and carcinoma) showed statistically significantly up-regulated CK19 (p = 0.012), decreased E-cadherin levels and distinctive patterns ofvimentin. CD44, CD56 and p53 were almost absent from parathyroid tissues. All carcinomas lacked parafibromin contrasting with invariable positivity in adenomas. Remarkable heterogeneity ofcell cycle markers and intermediate filaments must be accounted for in scientific studies and elaboration ofdiagnostic cut-offs.

Presence of the RET Cys634Tyr mutation and Gly691Ser functional polymorphism in Iranian families with multiple endocrine neoplasia type 2A.

Multiple Endocrine Neoplasia type 2A (MEN2A) is a complex autosomal dominant inherited syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and primary parathyroid hyperplasia. In patients with only one or two clinical features, identification of a germ line RET (REarranged in Transfection) mutation is required to make the diagnosis and initiate genetic counseling. We analyzed blood DNA from three Iranian families with three generations of MEN2A including 20 affected individuals with MTC and four with pheochromocytoma. RET hotspots were amplified in probands and sequenced for mutation detection. The causative mutation in all families was found to be the Cys634Tyr missense substitution. The presence of a functional SNP resulting in Gly691Ser was also detected in exon 11 of 15 affected cases. Four patients showed both of these RET variations. Our study shows that the Cys634Tyr missense substitution and the Gly691Ser polymorphism are recurrent in Iranian patients, since our families are unrelated. All asymptomatic carriers of the Cys634Tyr high-risk activating mutation were referred for prophylactic thyroidectomy.

Efficiency of (99)Tc(m)-sestamibi in diagnosis of parathyroid diseases with primary hyperparathyroidism

To evaluate the efficiency of (99)Tc(m)-sestamibi (MIBI) in the diagnosis of parathyroid diseases with primary hyperparathyroidism. One hundred and four cases with primary hyperparathyroidism underwent MIBI and parathyroidectomy between May 2010 to November 2013 were reviewed. With MIBI, single adenoma was found in 91 cases, two adenomas in 5 cases, carcinoma and hyperplasia in 3 cases respectively. Primary hyperparathyroidism was diagnosed based on the associated symptoms and signs in 93 patients, while it was indicated in 11 asymptomatic patients due to the presence of hypercalcemia in health examination. Parathroid hormone levels ranged from 98 to 2 800 ng/L, and serum calcium levels were between 2.56-4.23 mmol/L. The sensitivity of MIBI for total diseased parntyroids was 84.0% (100/119), and that for parathyroid adenoma, parnthyroid carcinoma, atypical adenoma and primary parathyroid hyperplasia was 87.1% (88/101), 3/3, 2/2 and 7/13, respectively. MIBI is efficient in the diagnosis of parathyroid diseases with primary hyperparathyroidism. The size and cystic degeneration of parathroid disease are two common factors decreasing MIBI reliability, and thyroid nodule is additional source leading to false-positive results.

Haemangioma of the Parathyroid Gland. Does it Really Exist?

We are reporting a case of a capillary haemangioma-like proliferation arising within a parathyroid gland adenoma, associated with primary hyperparathyroidism. The vessel proliferation bearing a close resemblance to a capillary haemangioma consisted of tightly packed capillaries, endothelial buds and occasional small caliber muscle-containing vessels. The observation expands the spectrum of tumour-associated vascular proliferations by adding an exuberant haemangioma-like pattern to its extreme end. These are a heterogeneous group of lesions reportedly induced by aberrant production of angiogenic factors. We investigated expression of VEGF, pKDR, FGF2, HIF1alpha and HIF2alpha and only VEGF gave a strong positive reaction in the adenoma cells entrapped in the vascular meshwork. Although this does not constitute a proof that aberrant VEGF production was a causative agent, unexpected supportive evidence for its pathogenic role emerged from a failure to detect chromogranin A. Chromogranin A is a precursor of several regulatory proteins, including vasostatin I, a multilevel suppressor of VEGF. The production of vasostatin I may have been reduced in a chromogranin A-negative adenoma which could lead to a loss of its opposing effect on VEGF-regulated processes. The only two other published cases of haemangioma of the parathyroid gland were reported in patients diagnosed with primary parathyroid hyperplasia with hyperparathyroidism, a pathophysiologic condition similar to our case. Therefore we raise the question whether these tumours could also represent a reactive phenomenon.

A Case of Coexistence of Parathyroid and Papillary Thyroid Carcinoma

Primary hyperparathyroidism is usually caused by a parathyroid adenoma, occasionally by primary parathyroid hyperplasia and rarely by parathyroid carcinoma. Coincidental occurrence of thyroid carcinoma in parathyroid adenoma is not uncommon, but synchronous parathyroid and thyroid carcinoma is extremely rare. Here, we describe a case of synchronous parathyroid carcinoma and papillary thyroid carcinoma. A 68-year-old female with no history of neck irradiation presented with hyperparathyroidism by parathyroid mass that was observed during the treatment of bronchiolitis obliterans organizing pneumonia. During the preoperative evaluation thyroid nodules were also observed. Therefore, she underwent surgery at Konyang University Hospital and was diagnosed with coexisting parathyroid and papillary thyroid carcinoma. (J Korean

Diagnostic strategies and surgical procedures in persistent or recurrent primary hyperparathyroidism.

The incidence of persistent or recurrent primary hyperparathyroidism reported in the literature lies between 1 and 10%. The main causes are represented by atypical locations or incorrect diagnosis of primary parathyroid hyperplasia. Since primary parathyroidectomy by an experienced surgeon has a success rate of 95%, there is no need for extended imaging studies prior to initial bilateral exploration. After confirming diagnosis of persistent or recurrent hyperparathyroidism exact localization studies are necessary. The most important procedures are ultrasonography, magnetic resonance imaging, technetium Tc99m sestamibi scintigraphy with a combined sensitivity of approximately 90%. In case of negative imaging results selective venous catheterization before reoperation can be performed. Reoperation by an experienced surgeon will be successful in 95% of cases.

Clinical analyses of 75 parathyroidectomy (PTE) patients and 69 adrenalectomy (AE) patients including saliva-type amylase-secreting secondary parathyroid hyperplasia (SPTH) and insulinoma with adrenal adenoma (AA) showing primary aldosteronism

Seventy-five parathyroidectomy (PTE) and 69 adrenalectomy (AE) patients were analyzed. The 75 PTE included 56 of secondary parathyroid hyperplasia (SPTH) with chronic renal failure (CRF) and 19 of primary parathyroid hyperplasia (PPTH) without CRF. The 69 AE included 23 with Cushing’s syndrome, 30 with primary aldosteronism, four with cortical carcinoma (three virilizing and one feminizing carcinomas), seven with pheochromocytoma (two multiple endocrine neoplasia 2A), two with paraganglioma, one with schwannoma, one with non-functional adenoma, and one with hepatic cancer metastasis. The 56 SPTH showed higher levels of intact (I)-parathyroid hormone (PT) of 1,359 ± 1,036 pg/ml than the 292 ± 372 pg/ml of the 19 PPTH. Measured vitamin D of 1, 25(OH)2D was higher in the nine PPTH (88.0 ± 34.7 pg/ml) than in the 46 SPTH (15.5 ± 13.9). High serum amylase of >350 IU/l and cyst formations were found in ten (18%) and 16 (29%) of the SPTH but none of the PPTH. At least ten (18%) of the SPTH had polycystic kidney disease (PKD). Saliva-type amylase of the SPTH resolved the high I-PTH. High levels (>6.0%) of Hb A1C (8.1%) were measured only in one SPTH case with mediastinal ectopic SPTH and PKD. High urine 17 ketosteroid (17 KS) levels of 161.5 ± 72.9 mg/l were measured in three virilizing carcinomas with metastases to the bone, liver, and/or lung. Low-grade feminizing carcinoma was observed in a 6-year-old boy. Cysts of the kidney and/or liver were found in 17 (74%) with Cushing’s syndrome, 12 (40%) with primary aldosteronism, and three (43%) with pheochromocytoma. One paraganglioma had liver and pancreatic cysts, and one schwannoma had polycystic ovary. High levels of Hb A1C were detected in six (26%) with Cushing’s syndrome, five (17%) with primary aldosteronism showing insulinoma, and two (29%) with pheochromocytoma. In all 13 patients with diabetes mellitus (DM), AE was an effective DM treatment.

Primary hyperparathyroidism: retrospective 10-year study of 32 cases.

Parathyroid glands are endocrine glands that regulate calcium metabolism. Usually four in number, they lie mostly on the posterior aspect of thyroid glands. Primary hyper-parathyroidism (PHPT) refers to a condition wherein they secrete an excess of parathyroid hormone leading to signs and symptoms of hypercalcemia. Thirty-two patients of primary hyper-parathyroidism were seen by us in the ten years. Majority of patients were below 40 years of age (88%). Male: female ratio was 1:4. The diagnosis was made incidentally in patients who reported for various signs and symptoms not responding to treatment. High serum calcium pointed to the diagnosis of primary parathyroid hyperplasia. It was confirmed by high level of serum parathyroid hormone and localization of enlarged parathyroid glands by USG / MRI and / or Tc-99 Technetium scan. Of the 32 patients examined, 43 parathyroid glands were excised, five cases had two glands excised; out of these 4 cases underwent parathyroid reimplantation in neck/forearm muscles. One unusual case underwent operation for giant-cell tumor of the head of humerus. This patient presented with excessive vomiting not responding standard medical management in post-operative period. During investigations serum calcium was found to be very high, the diagnosis was confirmed by finding high parathyroid hormone and corroborated by T(99) Technetium scan. Parathyroidectomy was done in all cases, of which 59% (18 cases) developed mild to severe tetany due to hypocalcaemia. Primary hyperplasia of thyroid gland is the most important cause of hypercalcemia. Hypercalcemia is found in all cases of PHPT in our series with high parathyroid hormone levels. Majority of our cases have one gland involvement and hypocalcaemia in our series is unusually high following excision of involved gland.

High resolution real time sonography of parathyroid tumors

A total of 15 patients with parathyroid tumours were scanned preoperatively using high-resolution real-time sonography (7 MHz). Of these, 14 had a single adenoma or primary hyperplasia, one had a carcinoma. In 13 out of 15 patients the echogenicity of the parathyroid tumours was consistently less than of the adjacent normal thyroid tissue; in 2 out of 15 cases parathyroid neoplasms were barely distinguishable in echogenicity from thyroid tissue. No specific echomorphologic differences were proved to exist between primary parathyroid hyperplasia, adenoma or carcinoma. The smallest parathyroid neoplasia in this study detected by sonography measured 5 x 8 mm in diameter. The value and limits of parathyroid sonography were discussed with regard to our own experience and the reports in the literature.

Mutational analysis of the PTH 3′‐untranslated region in parathyroid disorders

Sequence alterations in untranslated regions (UTRs) of genes are important contributors to human diseases, including hereditary thrombophilia, hereditary hyperferritinaemia-cataract and fragile X mental retardation syndromes. Recently, functional studies of the 3'-UTR of the PTH gene, encoding parathyroid hormone, have highlighted it as a potential target for pathogenic mutations in patients with parathyroid dysfunction. Regulation of PTH gene expression occurs in part through protein binding to a specific 26 nucleotide instability element in the 3'-UTR of PTH mRNA, in a sequence-dependent manner. Thus, the PTH 3'-UTR has emerged as an important potential contributor to parathyroid dysfunction. Therefore, we sought to rigorously examine the PTH 3'-UTR in patients with primary and secondary parathyroid disorders, including primary parathyroid hyperplasia, secondary parathyroid hyperplasia, sporadic parathyroid adenoma and familial hypoparathyroidism of unknown genetic basis. Twenty-one parathyroid glands from 14 patients with primary parathyroid hyperplasia, 40 sporadic parathyroid adenomas from 40 patients, 42 parathyroid glands from 29 patients with secondary parathyroid hyperplasia and peripheral blood leucocytes from 24 affected members of eight kindreds with familial hypoparathyroidism of unknown genetic basis were examined for mutations in the 3'-UTR of the PTH gene. No alterations from the normal sequence were detected in any of the 127 samples examined. Based on the absence of identifiable DNA sequence alterations in these forms of parathyroid dysfunction, it is unlikely that mutation of the PTH 3'-UTR contributes frequently to their pathogenesis.

Rare syndromes

Dermatologists may also encounter patients presenting with skin lesions that reflect an underlying endocrine disorder not commonly seen in daily practice. Some of these endocrine disorders include glucagonoma, neurofibromatosis type 1, McCune-Albright syndrome, multiple endocrine neoplasia, the Carney complex, carcinoid tumors, and mastocytosis. The clinical syndrome classically associated with glucagonoma includes necrolytic migratory erythema, weight loss, diabetes mellitus, anemia, cheilitis, venous thrombosis, and neuropsychiatric symptoms. The hallmarks of neurofibromatosis type 1 are the multiple café-au-lait spots and associated cutaneous neurofibromas. Other presenting features include freckling, peripheral neurofibromas, Lisch nodules, bone abnormalities, tumors, neurologic abnormalities and hypertension. McCune-Albright syndrome is characterized by café-au-lait spots, polyostotic fibrous dysplasia, sexual precocity, and hyperfunction of multiple endocrine glands. Multiple endocrine neoplasia type 2A is characterized by medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia. In some patients with multiple endocrine neoplasia type 2A, cutaneous lichen amyloidosis may also be present. Multiple endocrine neoplasia type 2B is characterized by medullary thyroid cancer and pheochromocytoma but not hyperparathyroidism. The syndrome also includes mucosal neuromas, typically involving the lips and tongue, intestinal ganglioneuromas and a marfanoid habitus. Multiple endocrine neoplasia type 1 is an autosomal dominant predisposition to tumors of the parathyroid glands (four-gland hyperplasia), anterior pituitary, and pancreatic islet cells; hence, the mnemonic device of the “3 Ps”; multiple cutaneous lesions (angiofibromas and collagenomas) are frequent in patients with multiple endocrine neoplasia type 1. Carney complex may be viewed as a form of multiple endocrine neoplasia because affected patients often have tumors of two or more endocrine glands, including primary pigmented nodular adrenocortical disease (some with Cushing's syndrome), pituitary adenoma, testicular neoplasms, thyroid adenoma or carcinoma, and ovarian cysts. Additional unusual manifestations include psammomatous melanotic schwannoma, breast ductal adenoma, and a rare bone tumor, osteochondromyxoma. Carcinoid syndrome is the term applied to a constellation of symptoms mediated by various humoral factors elaborated by some carcinoid tumors; the major manifestations are diarrhea, flushing, bronchospasm, and cardiac valvular lesions. Mast cell diseases include all disorders of mast cell proliferation. These diseases can be limited to the skin, referred to as “cutaneous mastocytosis,” or involve extracutaneous tissues, called “systemic mastocytosis.” Patients present with urticaria pigmentosa, mastocytoma, or diffuse cutaneous mastocytosis. Systemic involvement may be gastronintestinal, hematologic, neurologic, and skeletal.

Differential RNA Expression Profile by cDNA Microarray in Sporadic Primary Hyperparathyroidism (pHPT): Primary Parathyroid Hyperplasia versus Adenoma

Differential diagnosis between adenoma and hyperplasia in primary hyperparathyroidism (pHPT) remains a dilemma. The aim of this study was to assess differences in transcriptional genomic expression profiles between sporadic (nonfamilial) parathyroid hyperplasia (SPH), adenoma, and normal tissue. Parathyroid tissue from 12 patients with parathyroid adenoma, 3 with SPH, and 2 with normal glands was selected for analysis. Histopathology was reviewed in all cases, and all patients with adenomas presented normocalcemia for a minimum of 6 months after one gland resection. Hybridizations were performed in a microarray containing 19,968 human cDNA clones including contiguous replicates. Direct comparisons were performed with reverse labeling for every different pooled sample entity. Expression levels were analyzed using the SAM, SMA, LIMMA, Cluster, and PAM packages in the R environment for statistical computing. There were significant statistical differences between SPH and adenomas. In the direct comparison, a total of 200 genes showed differential expression (P < 0.03): 61 genes were upregulated (> 1.65-fold increase) and 139 were downregulated (> 1.58-fold decrease) with a B value > 4.68 (99.08% probability of real differential expression). When SPH was compared to normal parathyroid tissue, 50 genes were differentially expressed: 42 were upregulated (> 1.89) and 8 were downregulated (> 1.7) with a B > 4.26 (98.6% probability of real differential expression). At least 17 genes were differentially expressed and able to discriminate SPH from adenoma or normal tissue. Upregulated genes were related to apoptosis inhibition, cell proliferation, transcriptional activity and cell adhesion, among other activities. Downregulated genes were mainly related to ion channel activity, lipopolysaccharides, prostaglandin-d synthase, and integral membrane proteins. Our data suggest that SPH and adenoma have a singular molecular signature that, theoretically, could be used for the differential diagnosis of these entities and normal parathyroid tissue.

Angiogenesis and lymphangiogenesis in parathyroid proliferative lesions.

Angiogenesis and lymphangiogenesis are involved in tumoral growth and metastatic spread. There is little information on angiogenesis and no available data on lymphangiogenesis in parathyroid glands (PTG). Using immunohistochemistry for CD34, LYVE-1 (specific markers for vascular and lymphatic endothelium, respectively), vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, this study analyzes microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic growth factors in 13 normal PTG, 77 parathyroid adenomas (PTA), and 17 primary parathyroid hyperplasia (PPH). MVD was higher in PPH and PTA, compared with PTG (P < 0.001). There was no difference in VEGF-A expression among groups. In contrast, FGF-2 expression was higher in PPH, compared with PTA and PTG (P < 0.0001). FGF-2 scores and MVD were significantly correlated (r = 0.43). LVD did not differ among groups, and VEGF-C expression was unrelated to LVD. There was no relationship between MVD and tumor behavior (adenoma size, PTH, or calcium). In conclusion, this study shows increased angiogenesis in parathyroid proliferative lesions compared with normal glands and suggests that FGF-2 is proangiogenic in parathyroid tissue. In PTA, tumor behavior is not related to angiogenic phenotype. This is the first demonstration of lymphatic vessels in PTG, but the lack of correlation with VEGF-C expression suggests that VEGF-C is not the primary lymphangiogenic factor.

Primary Parathyroid Hyperplasia

Primary Parathyroid Hyperplasia

Deletion of 11q23 and Cyclin D1 Overexpression Are Frequent Aberrations in Parathyroid Adenomas

Hyperparathyroidism may result from parathyroid hyperplasia or adenoma, or rarely from parathyroid carcinoma. Pericentromeric inversion of chromosome 11 that results in activation of the P:RAD1/cyclin D1 gene and tumor suppressor gene loss have been described as genetic abnormalities in the evolution of parathyroid neoplasms. We studied tissue samples taken from primary parathyroid hyperplasia, parathyroid adenoma, and histologically normal parathyroid tissue by comparative genomic hybridization, fluorescent in situ hybridization, and immunohistochemistry for cyclin D1. DNA copy number changes were infrequent in primary hyperplasia (4 of 24, 17%), but common in adenomas (10 of 16, 63%; P: = 0.0059). The most common change was deletion of the entire chromosome 11 or a part of it, with a minimal common region at 11q23. This change was present in five (31%) adenomas and two (8%) primary hyperplasias. Fluorescent in situ hybridization confirmed the presence of both MEN1 alleles located at 11q13 despite deletion of 11q23 in all three cases studied. Cyclin D1 was overexpressed in six (40%) of the 15 adenomas studied, whereas none of the 27 hyperplasias (P: = 0.0010) nor the five histologically normal tissue samples overexpressed cyclin D1. Either DNA copy number loss or cyclin D1 overexpression was present in 13 (81%) of the 16 adenomas. We conclude that DNA copy number loss and cyclin D1 overexpression are common in parathyroid adenomas. The region 11q23 is frequently lost in parathyroid adenomas and occasionally in parathyroid hyperplasias, and this suggests the possibility that a tumor suppressor gene that is important in their pathogenesis is present on 11q23.

Refractory Renal Hyperparathyroidism: Clinical Features and Outcome of Surgical Therapy

Despite improvements in medical management parathyroidectomy has an important role in treatment of refractory renal hyperparathyroidism (HPT). The medical records of all patients who underwent parathyroidectomy from 1991 through 2000 were reviewed to determine the clinical and laboratory features and outcomes of treatment in patients with renal versus primary HPT. Twenty-one of 92 patients who underwent parathyroidectomy had renal HPT with a mean age of 47+/-3 years compared with 56+/-2 years for patients with primary HPT (P < 0.05). Clinical manifestations included osteodystrophy (19), pruritus (six), extraosseous calcification (three), and calciphylaxis (one). Parathyroid hormone, phosphorus, and alkaline phosphatase levels and weights of excised glands were higher in renal versus primary HPT (P < 0.05). Supernumerary glands were found in three patients (14%) with renal HPT and none of nine patients with primary parathyroid hyperplasia. After surgical therapy persistent or recurrent HPT occurred in three (14%) patients with renal and one (1.4%) patient with primary HPT (P < 0.05). Postoperative hypocalcemia occurred in 20 (95%) patients with renal HPT all of whom required intravenous calcium, compared with 25 (35%) patients with primary HPT (P < 0.05) of whom only three (4%) required intravenous calcium (P < 0.05). In contrast to those with primary HPT patients with renal HPT are younger and more likely to have severe osteodystrophy, postoperative hypocalcemia, and persistent or recurrent HPT.

Efficacy of preoperative dual-phase sestamibi scanning in hyperparathyroidism

Purpose: The objective of this article is to evaluate our experience with sestamibi scanning in patients with primary and secondary hyperparathyroidism. Patients and Methods: A retrospective review of patients referred to the radiology department at the University of Kansas Medical Center for parathyroid studies between January 1, 1993, and August 1, 1998, was done. Patients included in the study were those who underwent both dual-phase technetium (Tc-99m) sestamibi scanning and subsequent parathyroidectomy at our institution (n = 34). Twenty-six patients had primary hyperparathyroidism and 8 patients had secondary hyperparathyroidism. Fifteen had previous history of neck exploration. Results: Sensitivity of sestamibi scans in detection of all abnormal pathology in cases of primary hyperparathyroidism was 60% overall. Among the subset of adenoma cases, sensitivity was 82% (14/17). Among cases of primary parathyroid hyperplasia, no scan correctly localized all abnormal glands; however 60% (3/5) showed localization of at least one hyperplastic gland. Of the 2 patients with parathyroid carcinoma, in only one case was there evidence of sestamibi retention in the correct thyroid lobe. In patients with secondary hyperparathyroidism, sestamibi scanning was successful in identifying all hyperplastic tissue in only one case (sensitivity 13%). In 7 of the 8 cases of secondary hyperparathyroidism, the scan localized at least one hyperplastic gland. Conclusion: Sestamibi scanning is useful in the localization of abnormal pathology in cases of primary hyperparathyroidism, especially adenomas. In cases of hyperplasia, whether attributable to primary or secondary hyperparathyroidism, sestamibi imaging is less successful. (Am J Otolaryngol 2000;21:355-359. Copyright © 2000 by W.B. Saunders Company)

Intraoperative parathormone measurement in patients with multiple endocrine neoplasia type I syndrome and hyperparathyroidism.

Total or subtotal parathyroidectomy is considered the treatment of choice for multiple endocrine neoplasia type I (MEN-I)-associated primary hyperparathyroidism (HPT). However, persistent or recurrent HPT is frequently observed. The development of a rapid two-site immunoradiometric assay (IRMA) method for measuring intact parathormone (PTH) has provided a valuable tool for recognizing possible surgical failures. Our experience includes 16 MEN-I patients (10 females, 6 males) of mean age 35.5 years operated on between 1990 and 1996. Total parathyroidectomy (TPTX) with autotransplantation of parathyroid tissue was the standard treatment. Blood samples for PTH measurement were drawn at the induction of anesthesia (basal value), 10 and 20 minutes after the removal of each gland, and 60 minutes after TPTX. Rapid PTH measurement, which required only 15 minutes of incubation at 37 degrees C, showed a highly significant correlation (p < 0.0001) with the standard method. Circulating PTH levels exhibited a stepwise decrease during TPTX, reaching a mean value of 22.3% of the baseline 20 minutes after removal of the last gland. Two patients showed a prompt decrease of PTH after removal of the single enlarged gland, featuring the kinetics observed in the adenomas. One of these two patients was successfully treated with more conservative surgery. None of the patients showed persistence or recurrence of HPT. In our experience, intraoperative measurement of PTH seems to be a valuable adjunct in both the diagnosis of multiglandular involvement and the prediction of surgical treatment in patients with primary parathyroid hyperplasia.